Our main objective is to prepare inhibitors of protein biosynthesis and to study the mechanism of peptide bond formation at the ribosomal level. We plan to make a wide variety of structural modifications for use in mapping the ribosomal binding area at the peptidyl transferase (peptide forming) site. This will allow us to design molecules with maximum binding potential for the ribosome. Inhibition of protein synthesis offers great potential for the design of cancer chemotherapy agents. We plan to find different binding requirements among ribosomes from different sources which will enable us to prepare selective inhibitors of protein synthesis. BIBLIOGRAPHIC REFERENCES: "An Active Puromycin Analog Derived From a Non-Nephrotoxic Aminonucleoside" Robert Vince, Ronald G. Almquist, Clare L. Ritter, Frances N. Shirota, and Herbert T. Nagasawa, Life Science, 18, 345 (1976). "Partition of Ribosomes in Aqueous Two-Polymer Phase Systems" Sidney Pestka, David Weiss, and Robert Vince, Anal. Biochem., 71, 137 (1976).